Antibacterial and Bioregenerative Nanomaterials in Oral Health: From Material Design to Clinical Translation and Technological Trends
Abstract
1. Introduction
2. Materials and Methods
- Identification: The initial search generated a total of 485 records.
- Deduplication: After removing duplicates, 312 unique studies remained for evaluation.
- Screening: Titles and abstracts were screened against the inclusion criteria, resulting in 145 articles eligible for full-text analysis.
- Inclusion: A final number of 105 studies were included in the narrative synthesis. These were selected based on mechanistic relevance, consistency of reported data, and direct applicability to dental restorative procedures.
3. Antibacterial and Bioactive Nanomaterials for Restorative Dentistry
3.1. Context
3.2. Mechanisms of Action
3.3. Metallic Nanoparticle
3.4. Cationic Monomers and Natural Nanopolymers
3.5. Carbon-Based Nanomaterials
3.6. Integration into Composites and Adhesives
3.7. Limitations and Future Directions
4. Bioregenerative Nanomaterials in Restorative Dental Therapy
4.1. Concept and Biological Basis
4.2. Nanohydroxyapatite (nHAp)
4.3. Bioglass
4.4. Calcium Phosphates and Calcium Silicates
4.5. Hybrid Nanocomposites
4.6. Regenerative Mechanisms and Cellular Effects
4.7. Limitations and Future Directions
5. Dual-Function Nanomaterials with Antibacterial and Bioregenerative Activity
5.1. Concept and Rationale
5.2. Synergistic Action Mechanisms
5.3. NACP–DMAHDM Composites
5.4. Hybrid Systems of Ag–nHAp and ZnO–Bioglass
5.5. Chitosan- and Graphene-Based Nanocomposites
5.6. Smart Nanomaterials with Controlled Release
5.7. Cellular Compatibility and Biointegration
5.8. Clinical and Technological Perspectives
6. Technological Advances and Future Directions
6.1. Smart and Responsive Materials
6.2. Bioactive and Regenerative Nanomaterials
6.3. Digital and Additive Manufacturing
6.4. AI Integration
6.5. Sustainability and Regulatory Considerations
6.6. Future Directions
- To ensure repeatability and cross-study comparability, standardized experimental methods were developed to assess antibacterial activity, bioactivity, and mechanical performance.
- To evaluate long-term material stability using therapeutically relevant aging methods, such as thermocycling, prolonged water storage, and pH cycling, to determine the durability of antibacterial and bioactive functions.
- To implement sophisticated biofilm models with salivary pellicle development to better imitate intraoral microbial habitats.
- To support the integration of clinically significant objectives, such as secondary caries prevention, marginal integrity, restorative longevity, and biological safety.
7. Conclusions
- -
- Standardization: Implementation of rigorous testing protocols (e.g., ISO 10993) that include thermal and pH cycling;
- -
- Technology: Use of AI for formulation optimization and 3D printing for personalized regenerative structures;
- -
- Sustainability: Development of bio-fabricated materials based on natural compounds (e.g., nano-curcumin, chitosan) to minimize cytotoxicity risks;
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| ACP | Amorphous Calcium Phosphate |
| AgNPs | Silver Nanoparticles |
| AI | Artificial Intelligence |
| BAG | Bioactive Glass |
| BG | Bioglass |
| CS | Calcium Silicates |
| CuNPs | Copper Nanoparticles |
| DMAHDM | Dimethylaminohexadecyl Methacrylate |
| DMP-1 | Dentin Matrix Protein 1 |
| DSPP | Dentin Sialophosphoprotein |
| FDA | Food and Drug Administration |
| FDI | World Dental Federation |
| GO | Graphene Oxide |
| ISO | International Organization for Standardization |
| LS | Lithium Silicates |
| ML | Machine Learning |
| MPC | 2-Methacryloyloxyethyl Phosphorylcholine |
| NACP | Nano-Calcium Phosphate |
| nBG | Nanoscale Bioglass |
| nHAp | Nanohydroxyapatite |
| NCD | Non-Communicable Disease |
| PLGA | Poly(lactic-co-glycolic acid) |
| PCL | Polycaprolactone |
| QAM | Quaternary Ammonium Monomers |
| ROS | Reactive Oxygen Species |
| UV | Ultraviolet |
| ZnO NPs | Zinc Oxide Nanoparticles |
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| Main Category | Representative Examples | Primary Mechanism of Action | Clinical Applications and Relevant Effects | Key Limitations |
|---|---|---|---|---|
| Antibacterial Nanomaterials | AgNPs, ZnO, CuO, TiO2, Cationic monomers (DMAHDM), Chitosan, Graphene oxide | - Controlled release of metal ions (Ag+, Zn2+, Cu2+) - Generation of reactive oxygen species (ROS) - Contact-killing through electrostatic interactions - Inhibition of bacterial adhesion and biofilm formation | - Reduction in marginal secondary caries - Prevention of secondary inflammation - Incorporation into composites, cements, adhesives, and sealants | - Potential cytotoxicity at high concentrations - Discoloration (especially AgNPs) - Interference with polymerization - Long-term ion release stability |
| Bioregenerative Nanomaterials | Nanohydroxyapatite (nHAp), Bioglass (BG), Amorphous Calcium Phosphate (ACP, NACP), Calcium Silicates | - Release of Ca2+, PO43− and Si4+ ions - Promotion of secondary apatite nucleation - Stimulation of odontoblastic differentiation - Local pH buffering and rebalancing | - Remineralization of enamel and dentin - Support for dentin–pulp regeneration - Reduction in dentin hypersensitivity - Improved bonding at the dentin–adhesive interface | - Mechanical properties can be compromised at high filler loads - Release kinetics are difficult to control - Efficacy is highly dependent on the oral environment (pH, saliva) |
| Dual-Function Nanomaterials | NACP–DMAHDM, Ag–nHAp, ZnO–bioglass, Chitosan–GO, Zn- or F-doped bioglass | - Synergistic release of antibacterial and remineralizing ions- pH-responsive behavior (acid-triggered ion release) - Combined contact-killing effect and apatite formation | - “Smart” restorations with biologically adaptive behavior - Prevention of secondary caries and enhancement of tissue healing - Use in bioactive composites, cements, and base materials | - Complex formulation challenges - Balancing antimicrobial efficacy vs. cytotoxicity - Long-term durability and safety not yet established in clinical settings |
| Nanomaterial | Primary Antibacterial Mechanism | Major Advantages | Limitations/Challenges |
|---|---|---|---|
| Silver nanoparticles (AgNPs) | Release of Ag+ ions → denaturation of enzymatic proteins and disruption of the bacterial membrane; generation of reactive oxygen species (ROS) | Broad-spectrum antibacterial activity; rapid and persistent effect; good compatibility with resin composites | Potential cytotoxicity at higher concentrations; gray discoloration; incomplete understanding of biodistribution |
| Zinc oxide nanoparticles (ZnO NPs) | Release of Zn2+ and ROS generation → oxidative stress and inhibition of bacterial metabolism | Better biocompatibility than AgNPs; high chemical stability; synergistic effects with other agents | pH- and concentration-dependent antibacterial activity; potential interference with resin polymerization at higher loadings; variability in long-term ion release under oral conditions |
| Copper nanoparticles (CuNPs) | Release of Cu2+ → disruption of bacterial cell walls and inhibition of microbial DNA | Low cost; antibacterial and antifungal efficacy; good stability within composite matrices | Susceptible to oxidation and instability in moist environments; potential discoloration of the material |
| Titanium dioxide nanoparticles (TiO2 NPs) | Photocatalytic activation under UV or blue light → formation of bactericidal free radicals | Tunable photocatalytic properties; high stability; non-toxic in the absence of light | Require light activation; limited activity without irradiation; possible unwanted oxidative reactions |
| Cationic monomer DMAHDM | Contact killing—positively charged surfaces attract and disrupt bacterial membranes | Compatible with resin composites; long-lasting antibacterial effect; does not leach from the matrix | Active only upon direct contact; reduced efficiency in the presence of mature biofilm Contact-dependent antibacterial activity; reduced effectiveness against mature or thick biofilms; potential masking of cationic sites by salivary proteins and acquired pellicle formation |
| Chitosan (natural nanopolymer) | Electrostatic interaction with bacterial membranes → increased permeability and DNA inhibition | Excellent biocompatibility; biodegradable; additional anti-inflammatory properties | Low solubility at neutral pH; limited activity against Gram-negative bacteria |
| Graphene oxide (GO) | Mechanical membrane disruption (“cutting” effect) + ROS generation | Superior mechanical properties; synergistic effects with other agents; antibacterial activity without requiring metal ions | Potential pro-oxidative effects at high concentrations; biocompatibility still under investigation |
| Material | Composition | Mechanism of Action | Biological Effects | Primary Evidence Level |
|---|---|---|---|---|
| nHAp | Ca10(PO4)6(OH)2 | - Biomimetic nucleation - Ion release (Ca2+, PO43−) | - Enamel/dentin remineralization - Occlusion of dentinal tubules - Stimulation of odontogenic differentiation | In vitro, Animal model |
| Bioglass | SiO2–CaO–Na2O–P2O5 | - Apatite layer formation - Ion release (Ca2+, Si4+) - pH increase | - Dentin remineralization - Odontoblastic differentiation - Angiogenic potential | In vitro, Animal model |
| NACP | Amorphous Calcium Phosphate | - pH-responsive ion release - High surface reactivity | - Sustained remineralization - pH buffering capacity | In vitro |
| Calcium Silicates | CaSiO3, Ca3SiO5 | - Hydration reaction - Ca(OH)2 formation - Ion release | - Dentin bridge formation - Pulp capping applications - Antibacterial effect (high pH) | In vitro, Clinical trial (limited) |
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Pitic, D.E.; Nodiți-Cuc, A.-R.; Talpos-Niculescu, C.I.; Marian, D.; Popovici, R.A.; Kis, A.M.; Trusculescu, L.-M.; Feher, A.; Lile, I.E. Antibacterial and Bioregenerative Nanomaterials in Oral Health: From Material Design to Clinical Translation and Technological Trends. J. Funct. Biomater. 2026, 17, 87. https://doi.org/10.3390/jfb17020087
Pitic DE, Nodiți-Cuc A-R, Talpos-Niculescu CI, Marian D, Popovici RA, Kis AM, Trusculescu L-M, Feher A, Lile IE. Antibacterial and Bioregenerative Nanomaterials in Oral Health: From Material Design to Clinical Translation and Technological Trends. Journal of Functional Biomaterials. 2026; 17(2):87. https://doi.org/10.3390/jfb17020087
Chicago/Turabian StylePitic (Cot), Dana Emanuela, Aniela-Roxana Nodiți-Cuc, Cristina Ioana Talpos-Niculescu, Diana Marian, Ramona Amina Popovici, Andreea Mihaela Kis, Laria-Maria Trusculescu, Adina Feher, and Ioana Elena Lile. 2026. "Antibacterial and Bioregenerative Nanomaterials in Oral Health: From Material Design to Clinical Translation and Technological Trends" Journal of Functional Biomaterials 17, no. 2: 87. https://doi.org/10.3390/jfb17020087
APA StylePitic, D. E., Nodiți-Cuc, A.-R., Talpos-Niculescu, C. I., Marian, D., Popovici, R. A., Kis, A. M., Trusculescu, L.-M., Feher, A., & Lile, I. E. (2026). Antibacterial and Bioregenerative Nanomaterials in Oral Health: From Material Design to Clinical Translation and Technological Trends. Journal of Functional Biomaterials, 17(2), 87. https://doi.org/10.3390/jfb17020087

